Conversion surgery following immuno-chemotherapy in initially-unresectable esophageal squamous cell carcinoma: A real-world multicenter study.
Authors: Shujie Huang, Hansheng Wu, Chao Cheng, Ming Zhou, Enwu Xu, Wanli Lin, Guangsuo Wang, Jiming Tang, Xiaosong Ben, Dongkun Zhang, Liang Xie, HaiYu Zhou, Gang Chen, Weitao Zhuang, Yong Tang, Fangping Xu, Junhui Fu, Guibin Qiao
Journal: Journal of Clinical Oncology (2022)

e16045 Background: Currently, the real-world evidence is not available to support the practice of induction immunochemotherapy (iIC) plus conversion surgery for initially-unresectable esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the feasibility, safety and effectiveness of conversion surgery following iIC for advanced ESCC in a real-world scenario. Methods: In this multi-center, single-arm, real-world study (NCT04822103), patients who had unresectable cT4b ESCC tumors with evident involvement of the adjacent organs (aorta, trachea, or bronchus) or had multi-station, bulky lymphadenopathy were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every three weeks. Radiologcal assessment was performed for patients who completed at least two cycles of immunochemotherapy. In general, patients with significant relief of cancer-related clinical symptoms and radiological complete response/partial response disease were deemed surgical candidates. The primary endpoints were the objective response rate (ORR) per RECIST version 1.1 and safety profile per CTCAE version 5.0. Results: Between Nov 2019 and June 2021, 155 patients were enrolled in the final analysis. The numbers of patients with pre-treatment clinical stage III, and IVA were 21 (13.5%) and 134 (86.5%), respectively. Upon the completion of preoperative treatment, 6 (3.9%) patients achieved radiological complete response (CR), 92 (59.4%) achieved partial response (PR), and 45 (29.0%) achieved stable disease (SD), yielding an ORR and DCR of 63.3% and 92.3%, respectively. Esophagectomy was then offered to 116 patients who were considered suitable for surgery, yeilding a conversion rate of 74.8%. 109 out of 116 patients achieved R0 resection. Pathological complete response (pCR) of the primary tumor was observed in 26 (22.4%) patients, with 25 (21.6%) of them achieving pCR in both primary tumor and metastatic lymph nodes. Most patients (111/116, 95.7%) had a downstaging in tumor invasion depth. However, downstaging of nodal metastasis was observed in 48 (48/116, 41%) patients. Thirteen patients (13/116, 11.2%) had progressive nodal response. Among the treated patients, 69.0% (107/155) patients experienced at least one treatment-related adverse event (TRAEs), while 29% (49/155) had grade three or higher (G ≥ 3) TRAEs, including leukopenia (20/155, 12.9%), neutropenia (18/155, 11.6%), rash (12/155, 7.7%), diarrhea (6/155, 3.9%), and infection (6/155, 3.9%). Conclusions: We demonstrated that conversion surgery following immunochemotherapy is feasible, safe and effective for initially-unresectable ESCC patients. Further larger-scale studies are needed to establish the standard-of-care use of iIC in the preoperative settings for initially-unresectable ESCC patients.